Biology subjects

Tanaka, E. M.

Publications and source records attributed to Tanaka, E. M..

23 records · Page 2Linked to original sources

bioRxiv2021

Tig1 regulates proximo-distal identity during salamander limb regeneration

Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an awareness of their spatial location, a property termed positional identity. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/Rarres1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting Hoxa13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.

developmental biology↗

bioRxiv2020

Modeling the spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modelling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during 85 hours after amputation within ~830{square}m of the injury. We adapted FUCCI technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.

bioinformatics↗

bioRxiv2019

Metabolic control of YAP via the acto-myosin system during liver regeneration

The mechanisms of organ size control remain poorly understood. A key question is how cells collectively sense the overall status of a tissue. We addressed this problem focusing on mouse liver regeneration, which is controlled by Hippo signalling. Using digital tissue reconstruction and quantitative image analysis, we found that the apical surface of hepatocytes forming the bile canalicular network expands concomitant with an increase of F-actin and phospho-Myosin, to compensate an overload of bile acids. Interestingly, these changes are sensed by the Hippo transcriptional co-activator YAP, which localizes to the apical F-actin-rich region and translocates to the nucleus in dependence of the acto-myosin system. This mechanism tolerates moderate bile acid fluctuations under tissue homeostasis, but activates YAP in response to sustained bile acid overload. Using an integrated biophysical-biochemical model of bile pressure and Hippo signalling, we explained this behaviour by the existence of a mechano-sensory mechanism that activates YAP in a switch-like manner. We propose that the apical surface of hepatocytes acts as a self-regulatory mechano-sensory system that responds to critical levels of bile acids as readout of tissue status.

systems biology↗

bioRxiv2019

The Prrx1 limb enhancer marks an adult population of injury-responsive, multipotent dermal fibroblasts

The heterogeneity of adult tissues has been posited to contribute toward the loss of regenerative potential in mammals. Here we characterize an adult population of dermal fibroblasts that maintain expression of a Prrx1 enhancer which originally marked mesenchymal limb progenitors. Prrx1 enhancer-positive cells (Prrx1enh+) make up a small subset of adult dermal cells (~0.2%) and reside mainly within specific dermal perivascular and hair follicle niches. Upon injury, however, Prrx1enh+ cells readily migrate into the wound bed and amplify on average 16-fold beyond their uninjured numbers. Additionally, Prrx1enh+ cells emigrate out of their dermal niches following wounding and contribute to subcutaneous tissue. Prrx1enh+ cells are uniquely injury-responsive and do not contribute to tissue homeostasis or enriched by neonatal-like Wnt signaling. Prrx1enh+ cells represent a potent regenerative cell population that, despite being a meager minority in adult skin, demonstrate the potential to tip the balance of mammalian wound healing toward scar-free healing.

developmental biology↗

bioRxiv2018

Broad applicability of a streamlined Ethyl Cinnamate-based clearing procedure

Turbidity and opaqueness are inherent properties of tissues which limit the capacity to acquire microscopic images through large tissues. Creating a uniform refractive index, known as tissue clearing, overcomes most of these issues. These methods have enabled researchers to image large and complex 3D structures with unprecedented depth and resolution. However, tissue clearing has been adopted to a limited extent due to a combination of cost, time, complexity of existing methods and potential negative impact on fluorescence signal. Here we describe 2Eci (2nd generation Ethyl cinnamate based clearing method) which can be used to clear a wide range of tissues, including cerebral organoids, Drosophila melanogaster, zebrafish, axolotl, and Xenopus laevis in as little as 1-5 days while preserving a broad range of fluorescence proteins including GFP, mCherry, Brainbow, and alexa-fluorophores. Ethyl cinnamate is non-toxic and can easily be used in multi-user microscope facilities. This method will open up clearing to a much broader group of researchers, due to its broad applicability, ease of use, and non-toxic nature of Ethyl cinnamate.\n\nSummary statementThe non-toxic, broadly applicable, and simplified protocol of 2Eci tissue clearing makes it possible for non-specialist labs to use clearing approaches on conventional inverted microscopes.

developmental biology↗